GLUCOSE REPRESSION DEREPRESSION IN BUDDING YEAST - SNF1 PROTEIN-KINASE IS ACTIVATED BY PHOSPHORYLATION UNDER DEREPRESSING CONDITIONS, AND THIS CORRELATES WITH A HIGH AMP-ATP RATIO/
Wa. Wilson et al., GLUCOSE REPRESSION DEREPRESSION IN BUDDING YEAST - SNF1 PROTEIN-KINASE IS ACTIVATED BY PHOSPHORYLATION UNDER DEREPRESSING CONDITIONS, AND THIS CORRELATES WITH A HIGH AMP-ATP RATIO/, Current biology, 6(11), 1996, pp. 1426-1434
Background: Genetic studies of Saccharomyces cerevisiae have shown tha
t Snf1p and Snf4p, which together form the SNF1 complex, are essential
for gene derepression on removal of glucose from the medium. However
the metabolic signal(s) involved, and the exact role of SNF1, have rem
ained enigmatic. Recently, the AMP-activated protein kinase (AMPK) was
shown to be the mammalian homologue of SNF1.AMPK is activated by the
elevation of the cellular AMP:ATP ratio, which occurs during cellular
stress in mammalian cells. The mechanism of activation involves phosph
orylation of AMPK by an upstream protein kinase (AMPKK). We have inves
tigated whether a similar mechanism might explain the role of SNF1 in
yeast in the response to the stress of glucose starvation. Results: Th
e protein kinase activity of SNF1 was dramatically and rapidly activat
ed by phosphorylation on removal of glucose from the medium. SNF1 was
not activated directly by AMP, but could be inactivated by protein pho
sphatases and reactivated by mammalian AMPKK, We also demonstrated tha
t an endogenous SNF1-reactivating factor, most likely an upstream prot
ein kinase, is present in yeast extracts. Under a variety of different
growth conditions, there was a correlation between cellular adenine n
ucleotide levels and the activation slate of SNF1. Conclusions: Apart
from the lack of direct allosteric activation of SNF1 by AMP, the regu
lation of the mammalian AMPK and yeast SNF1 protein kinase cascades is
highly conserved. Adenine nucleotides are now good candidates for met
abolic signals which indicate the lack of glucose in the medium, trigg
ering activation of SNF1 and derepression of glucose-repressed genes.